An important therapeutic issue in neuropsychiatric disease, particularly in geriatric patients, is the variability in treatment response and the inability to predict treatment outcome. Decreased monoaminergic responsiveness may be a potential neurobiologic mechanism underlying treatment resistance across several neuropsychiatric disorders. The overarching theme of the candidate's funded research in AD, schizophrenia and geriatric depression is that decreased monoaminergic responsiveness is related to treatment resistance. To evaluate monoaminergic function in vivo, the candidate has developed methods using Positron Emission Tomography (PET) imaging, radiotracers for neurotransmitter receptors and pharmacologic challenges. This application of PET methodology represents the most direct, non-invasive and quantitative method of measuring neurotransmitter activity in the living human brain. The PET studies performed thus far have consistently demonstrated substantial between subject variability in monoamine responsiveness in normal controls and in patients. Variability of monoamine responsiveness has been observed also in pharmacologic challenge studies using behavioral and neuroendocrine outcome measures. The goals of this Independent Scientist Award are to obtain training in methods complementary to brain imaging techniques that will enable the candidate to better interpret the variability in monoaminergic responsiveness observed in the PET data. The goals of the training experience are to incorporate genetic markers of monoamine receptor and transporter alleles and polysomnographic methods into her existing research program and to obtain training in the neuroanatomy of cholinergic and monoaminergic interactions and neuroimaging in affective disorders. The research plan is conducted within the framework of three funded studies to use PET to investigate 1) serotonin-dopamine interactions in schizophrenia; 2) cholinergic modulation of monoamine function in Alzheimer's Disease; and 3) the effects of sleep deprivation and antidepressant treatment on cerebral glucose metabolism in geriatric depression. These studies are designed to relate alterations in monoamine responsiveness to subsequent therapeutic response. The long term goal of the candidate's research is to understand the neurobiologic substrates of treatment resistance in neurodegenerative disorders and to use the genetic, polysomnographic and imaging data to predict the course of pharmacotherapy. The Independent Scientist Award will enable the candidate to firmly focus her research in the area of geriatric neuropsychiatry.
| Marano, Christopher M; Workman, Clifford I; Lyman, Christopher H et al. (2015) Structural imaging in late-life depression: association with mood and cognitive responses to antidepressant treatment. Am J Geriatr Psychiatry 23:4-12 |
| Sankar, Tejas; Chakravarty, M Mallar; Bescos, Agustin et al. (2015) Deep Brain Stimulation Influences Brain Structure in Alzheimer's Disease. Brain Stimul 8:645-54 |
| Hirao, Kentaro; Smith, Gwenn S (2014) Positron emission tomography molecular imaging in late-life depression. J Geriatr Psychiatry Neurol 27:13-23 |
| Marano, Christopher M; Workman, Clifford I; Lyman, Christopher H et al. (2014) The relationship between fasting serum glucose and cerebral glucose metabolism in late-life depression and normal aging. Psychiatry Res 222:84-90 |
| Marano, Christopher M; Workman, Clifford I; Kramer, Elisse et al. (2013) Longitudinal studies of cerebral glucose metabolism in late-life depression and normal aging. Int J Geriatr Psychiatry 28:417-23 |
| Smith, Gwenn S; Laxton, Adrian W; Tang-Wai, David F et al. (2012) Increased cerebral metabolism after 1 year of deep brain stimulation in Alzheimer disease. Arch Neurol 69:1141-8 |
| Munro, Cynthia A; Workman, Clifford I; Kramer, Elisse et al. (2012) Serotonin modulation of cerebral glucose metabolism: sex and age effects. Synapse 66:955-64 |
| Ajilore, Olusola; Smith, Gwenn S (2011) Neuroimaging in geriatric psychiatry: integrative research as the next frontier. Am J Geriatr Psychiatry 19:1-3 |
| Bruce, Martha L; Bartels, Stephen J; Lyness, Jeffrey M et al. (2011) Promoting the transition to independent scientist: a national career development program. Acad Med 86:1179-84 |
| Smith, Gwenn S; Kahn, Alan; Sacher, Julia et al. (2011) Serotonin transporter occupancy and the functional neuroanatomic effects of citalopram in geriatric depression. Am J Geriatr Psychiatry 19:1016-25 |
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